Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China.
Fujian Academy of Integrative Medicine, Fuzhou, Fujian, China.
PLoS One. 2019 Aug 12;14(8):e0220846. doi: 10.1371/journal.pone.0220846. eCollection 2019.
Inflammatory cytokines enhanced the progress of the pathogenesis of osteoarthritis, however the mechanisms remain unclear. The objective is to determine aquaporins (AQPs) in the pathogenesis of osteoarthritis.
Primary rat articular chondrocytes were treated with IL-1β to mimic the early stage of osteoarthritis in vitro. Early osteoarthritis animal model was established by intra-articular injection of 4% papain. Micro- or ultra-structure histopathologic changes, cell viability, apoptosis cells and cell membrane permeability, locations and expressions of AQP1 and AQP3 and matrix were detected in the cartilage or in the chondrocytes of knee. IL-1β could reduce the chondrocytes viability, increase the apoptosis cells, and also impair the cell membrane and organelles. IL-1β significantly induced the up-regulation of AQP1 and AQP3 in the chondrocytes. In the chondrocytes, AQPs were mainly clustered in both membrane and perinuclear region of cytoplasm, while higher AQPs were detected in the superficial and middle layers of the cartilage. With the up-regulation of AQPs, the cartilage matrix was considerably decreased in both the chondrocytes and in the osteoarthritis cartilage. In the early osteoarthritis rat model, serum and synovial fluid confirmed that higher IL-1β could increase the expressions of AQPs, and decrease the cartilage matrix in both the chondrocytes and the cartilage.
Inflammatory cytokine IL-1β via up-regulation of AQPs caused the abnormal metabolism of water transport and loss of the cartilage matrix in the chondrocytes, and ultimately exacerbated the pathogenesis of early osteoarthritis. Therefore, AQPs may be a candidate therapeutic target for prevention and treatment of osteoarthritis.
炎症细胞因子增强了骨关节炎发病机制的进展，但机制尚不清楚。目的是确定水通道蛋白（AQP）在骨关节炎发病机制中的作用。
原代大鼠关节软骨细胞用白细胞介素-1β（IL-1β）处理，以模拟体外骨关节炎的早期阶段。通过关节内注射 4%木瓜蛋白酶建立早期骨关节炎动物模型。在膝关节软骨或软骨细胞中检测微结构或超微结构组织病理学变化、细胞活力、凋亡细胞和细胞膜通透性、AQP1 和 AQP3 的位置和表达以及基质。IL-1β 可降低软骨细胞活力，增加凋亡细胞，并损害细胞膜和细胞器。IL-1β 显著诱导软骨细胞中 AQP1 和 AQP3 的上调。在软骨细胞中，AQP 主要聚集在细胞质的膜和核周区域，而在软骨的浅层和中层检测到更高的 AQP。随着 AQP 的上调，软骨基质在软骨细胞和骨关节炎软骨中均显著减少。在早期骨关节炎大鼠模型中，血清和滑膜液证实，更高水平的 IL-1β 可增加 AQP 的表达，并减少软骨细胞和软骨中的软骨基质。
炎症细胞因子白细胞介素-1β通过上调 AQP 引起水转运异常和软骨细胞中软骨基质的丢失，最终加剧了早期骨关节炎的发病机制。因此，AQP 可能是预防和治疗骨关节炎的候选治疗靶点。
